Analysis of histocompatibility requirements for proliferative and helper T cell activity. T cell populations depleted of alloreactive cells by negative selection.

T cell populations were prepared from donors immunized with hapten-carrier conjugates and were depleted of alloreactive cells by negative selection. This was accomplished by injection of the cells into H-2-disparate irradiated recipients and recovery from the thoracic duct after 18-40 h. The genetic requirements for the proliferative and helper activity of these populations was determined. The proliferative response to antigen presented on adherent, Thy-1-negative cells was determined, and a requirement for syngeneic antigen-presenting cells (APC) was demonstrated. The same T cells were assayed for their ability to give help to hapten primed B cells. It was shown that there was a requirement for syngeneic APC and for linked recognition of hapten and carrier determinants on the same molecule by the B cell and T cell. There was no requirement for the B cell to be H-2 compatible with the T cell. The requirement for linked recognition was taken as evidence that the responses in allogeneic combinations were not a result of positive allogeneic effects. Precisely comparable restrictions were found with positively selected cells.